Volume-regulated anion channel subunit LRRC8E

Definition:

Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes. The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine. Mediates efflux of amino acids, such as aspartate, in response to osmotic stress. The VRAC channel also mediates transport of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol. Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition. Also plays a role in lysosome homeostasis by forming functional lysosomal VRAC channels in response to low cytoplasmic ionic strength condition: lysosomal VRAC channels are necessary for the formation of large lysosome-derived vacuoles, which store and then expel excess water to maintain cytosolic water homeostasis.

References:

[1]. Lauren J Lahey, et al. LRRC8A:C/E Heteromeric Channels Are Ubiquitous Transporters of cGAMP. Mol Cell. 2020 Nov 19;80(4):578-591.e5. [Content Brief]

[2]. Ruhma Syeda, et al. LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength. Cell. 2016 Jan 28;164(3):499-511. [Content Brief]

[3]. Felizia K Voss, et al. Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. Science. 2014 May 9;344(6184):634-8. [Content Brief]

[4]. Darius Lutter, et al. Selective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels. J Cell Sci. 2017 Mar 15;130(6):1122-1133. [Content Brief]

[5]. Ping Li, et al. LRRC8 family proteins within lysosomes regulate cellular osmoregulation and enhance cell survival to multiple physiological stresses. Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):29155-29165. [Content Brief]

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